Clinical parameters predicting survival duration after hepatectomy for intrahepatic cholangiocarcinoma

BACKGROUND:

Currently, the most effective treatment for intrahepatic cholangiocarcinoma (ICC) is complete hepatic tumour excision.

OBJECTIVE:

To identify the clinical parameters associated with survival duration for ICC patients following hepatectomy, and to construct a mathematical model for predicting survival duration.

METHODS:

Demographic data and clinical variables for 102 patients diagnosed with ICC, who underwent exploratory laparotomy at a single centre from July 1998 to December 2000 and were followed for an average of 24 months, were collected in 2011. Patients were randomly assigned into training (n=76) and validation (n=26) groups. Univariate and multivariate analyses were performed to identify factors associated with posthepatectomy survival duration.

RESULTS:

Univariate analysis revealed that more than three lymph node metastases, a serum carbohydrate antigen 19-9 level >37 U/mL, stage IVa tumours, and intra- or perihepatic metastases were significantly associated with decreased survival duration. Curative resection was significantly associated with increased survival duration. A mathematical model incorporating parameters of age, sex, metastatic lymph node number, curative surgery, carbohydrate antigen 19-9 concentration, alpha-fetoprotein concentration, hepatitis B, TNM stage and tumour differentiation was constructed for predicting survival duration. For a survival duration of less than one year, the model exhibited 93.8% sensitivity, 92.3% total accuracy and a positive predictive value of 93.8%; for a survival duration of one to three years, the corresponding values were 80.0%, 69.2% and 57.1%, repsectively.

CONCLUSIONS:

The mathematical model presented in the current report should prove to be useful in the clinical setting for predicting the extent to which curative resection affects the survival of ICC patients, and for selecting optimal postoperative treatment strategies.     

Repeated hepatectomy for recurrent intrahepatic cholangiocarcinoma: report of two cases

Repeated hepatectomy for remnant liver recurrence of primary intrahepatic cholangiocarcinoma (ICC) is a seldom-encountered surgical technique because of its poor prognosis. Here, we present two long-term survivors of recurrent ICC by repeated hepatectomy. One patient underwent five hepatectomies in 6 years; first, extended left hepatectomy for a primary mass-forming-type ICC and then four partial hepatectomies for independent recurrent tumors all developing in segment V. The other patient underwent re-hepatectomy for a very large recurrent tumor 7 years after the first left hepatectomy for a primary periductal-infiltrating-type ICC; and has survived for approximately 2 years from the second operation under hepatic arterial infusion chemotherapy. The recurrent tumor in the latter case arose in the segment IV remnant corresponding to the cut margin of the liver after the first inappropriate left hepatectomy. The mode of hepatic recurrence seemed closely related to the portal segmentation: in the first case, intrahepatic metastases via portal tributaries; and in the second, the occult residual cancer spreading widely through bile ductules.     

Predictive factors of recurrence for patients with intrahepatic cholangiocarcinoma after hepatectomy

Background/Aims: To identify risk factors related to postoperative recurrence for intrahepatic cholangiocarcinoma (ICC) patients with negative resection margin. Methodology: A total of 64 ICC patients who underwent resection with negative margin at our center from 2002 to 2010 were recruited in the present study. All clinicopathological characteristics were assessed using univariate analyses. Independent risk factors were identified by Cox regression. Factors significant at a p<0.10 in the univariate analyses were involved in the multivariate analyses. The diagnostic accuracy of the identified risk factors was evaluated using receiver operating curve (ROC). Results: The overall 1-, 3- and 5-year recurrence-free survival rates for patients with ICC were 63%, 32% and 27%, respectively. The most common site of postoperative recurrence was the liver. Lymph node metastasis, perineural invasion and total tumor size greater than 5cm showed prognostic power in multivariate analysis. The recurrence-free survival rates reduced with the increasing of the number of risk factor for patients with ICC. Conclusions: This study suggested liver was the most common recurrence site and confirmed lymph node metastasis, perineural invasion and total tumor size greater than 5cm may be associated with poor outcome for ICC patients with negative resection margin.     

Patient outcome and prognostic factors in intrahepatic cholangiocarcinoma after hepatectomy

BACKGROUND/AIMS: The present study was designed to provide a systematic analysis of prognosis of patients who underwent hepatic resection for intrahepatic cholangiocarcinoma (ICC). METHODOLOGY: Subjects were 36 consecutive ICC patients who had undergone hepatic resection between 1994 and 2005. The analyzed factors included various clinicopathological and surgical parameters, counts of microvessel stained for CD34 and expression of proliferative cell nuclear antigen. RESULTS: The 1, 2, 3-year disease-free survival rates after surgery were 33, 18, and 0% and the 1, 3 and 5-year overall survival rates were 45, 29, and 8%. High CEA levels (> or = 10 ng/mL), excessive intraoperative blood loss (> or = 1000 mL) and presence of neighboring peritoneal dissemination were significantly associated with shorter disease-free survival (p < 0.05). High CEA levels, periductal invasion type, excessive intraoperative blood loss and non-fibrotic liver were significant factors associated with shorter overall survival (p < 0.05). Multivariate Cox proportional hazards regression model identified high CEA values, periductal invasive type, excessive intraoperative blood loss and non-fibrotic liver as significant and independent determinants of poor prognosis. CONCLUSIONS: Hepatic resection with minimal blood loss followed by close follow-up is a suitable strategy for management of ICC patients with poor prognostic factors.     

腹腔镜肝切除术与开腹肝切除术治疗肝内胆管细胞癌患者短期临床疗效研究

目的 研究腹腔镜肝切除术(LH)与开腹肝切除术(OH)治疗肝内胆管细胞癌(ICC)患者的短期临床疗效。方法 2018年2月～2021年2月我院诊治的122例ICC患者,被随机分为对照组61例和观察组61例,分别接受OH或LH治疗,随访观察半年。采用ELISA法检测血清C反应蛋白(CRP)、皮质醇(Cor)和白细胞介素-6(IL-6)。结果 LH组手术时长、术中失血量、肛门首次排气和术后住院日分别为(232.2±50.4)min、(592.3±164.7)ml、(2.1±0.8)d和(6.5±1.3)d,显著短于或少于0H组【分别为(321.1±69.7)min、(995.5±321.4)ml、(2.7±0.7)d和(8.2±1.7)d,P<0.0 5】;在术后3 d时,LH组血清CRP、Cor和IL-6水平分别为(25.1±4.0)mg/L、(529.6±75.4)mmol/L和(83.5±7.2)pg/ml,均显著低于0H组【分别为(39.8±5.1)mg/L、(654.7±78.1)mmol/L和(97.3±10.2)pg/ml,P<0.05】;在术后7 d时,LH组血...     

Recurrent intrahepatic cholangiocarcinoma: single-center experience using repeated hepatectomy and radiofrequency ablation

Background

Intrahepatic cholangiocarcinoma (IHC) is a rare liver malignancy with a rising incidence worldwide. Since no standard treatment has been established so far, the aim of this study was to assess the safety and efficacy of repeated liver resection and/or radiofrequency ablation (RFA) in selected cases with recurrent IHC.

Patients and methods

The outcome of 13 patients who had been treated at least once for recurrent IHC by repeated liver resection and/or RFA was retrospectively analyzed. A total of 12 repeated liver resections and 8 radiofrequency ablations were performed in these patients between 2002 and 2008.

Results

After a median follow-up period of 28 months after primary liver resection (12–69 months), seven patients (54%) are still alive and three of these patients (23% of the entire cohort) are regarded as disease-free. The median survival for all patients was 51 months (12–69 months). One- and three-year survival after primary surgery was 92 and 52%, respectively, with an overall complication rate of 7.6%.

Conclusion

According to the present data, repeated liver resection and radiofrequency ablation are feasible in select patients with recurrent IHC. Both procedures can be regarded as safe and might lead to a prolongation of patient survival.     

Postoperative survival in intrahepatic cholangiocarcinoma showing intraductal growth

Clinicopathologic variables favoring recurrence after hepatic resection for intrahepatic cholangiocarcinoma showing intraductal growth remain unclear. We investigated various clinicopathologic features in three patients who underwent resection for this type of intrahepatic cholangiocarcinoma. All underwent extended left hepatectomy plus resection of the caudate lobe and lymph node dissection. Lymph nodes showed no pathologic involvement. Although no cancer cells were seen in the mucosal layer by intraoperative pathologic examination at the bile duct stump in any patient, pathologic examination of resected specimens showed cancer cells invading beyond the mucosal layer in connective tissues surrounding the bile duct stump (interstitial invasion) of the Glisson's sheath in 2 patients. One of them died of cancer recurrence near the bile duct stump, while the third patient, without interstitial invasion, has survived for 10.6 years. In the intraductal growth type of intrahepatic cholangiocarcinoma, absence of cancer cells should be confirmed by intraoperative pathologic examination of not only the mucosal layer of the bile duct but also the connective tissue surrounding the bile duct, since interstitial invasion may be a risk factor for cancer recurrence.     

Oncological relevance of major hepatectomy with inferior vena cava resection for intrahepatic cholangiocarcinoma

BackgroundThis study aimed to investigate the short- and long-terms outcomes of patients undergoing major hepatectomy (MH) with inferior vena cava (IVC) resection for intrahepatic cholangiocarcinoma (ICC).MethodsData from all patients who underwent MH for ICC with or without IVC resection between 2010 and 2018 were analysed retrospectively. Postoperative outcomes, overall survival (OS), and recurrence-free survival (RFS) were compared in the whole population. A propensity score matching (PSM) analysis and an inverse probability weighting analysis (IPW) were performed to assess the influence of IVC resection on short- and long-terms outcomes.ResultsAmong the 78 patients who underwent MH, 20 had IVC resection (IVC patients). Overall, the mortality and severe complication rate were 8% and 20%, respectively. IVC patients required more extended hepatectomies (p = 0.001) and had increased rates of transfusions (p = 0.001), however they did not experience increased postoperative morbidity, even after PSM. The 1-, 3- and 5-years OS and DFS were 78%, 45%, and 32% and 48%, 20%, and 16%, respectively. IVC was not associated with decreased OS (p = 0.52) and/or RFS (p = 0.85), even after IPW.ConclusionMH with IVC resection for ICC seems to provide acceptable short- and long-term results in a selected population of patients.     

Long-term survival and prognostic factors in the surgical treatment for intrahepatic cholangiocarcinoma

Background/Purpose. We retrospectively investigated the clinicopathologic features and outcome of 51 patients who underwent hepatectomy for intrahepatic cholangiocellular carcinoma (ICC) between 1991 and 2000, and we also analyzed the potential prognostic factors for long-term survival. Methods. There were 27 men and 24 women, with a mean age of 63.7 years. The surgical procedures were extended right or left hepatectomy (15 cases), right or left hepatectomy (19 cases), bisegmentectomy (3 cases), segmentectomy (7 cases), and subsegmentectomy (7 cases). The macroscopic findings of the excised tumor showed the mass-forming (MF) type (31 cases), the periductal-infiltrating (PI) type (13 cases), and the intraductal growth (IG) type (7 cases). Results. The patients with the MF type had a significantly higher incidence of lymph node metastasis (44.8%), as compared to those with the PI or IG type (15.0%). Two patients who died of hepatic failure during their hospital stay were excluded from this survival study. The cumulative 1-, 3-, and 5-year survival rates in 49 patients who underwent liver resection were 68.2%, 44.1%, and 32.4%, respectively. The patients with the IG type had the best outcome, followed by those with the PI type and MF type. The survival rates with or without lymph node metastasis were 9.0% and 60.6% at 3 years, and 9.0% and 42.9% at 5 years, respectively (P ? 0.05). The 1-, 2-, and 3-year survival rates in the MF-type patients with lymph node metastasis were 25.4%, 16.9%, and 0%, respectively. Eight patients (15.7%) survived for more than 5 years after operation. The gross appearance of these tumors was the PI type in 5 patients, the IG type in 2, and the IG + MF type in 1. Except for one case with the PI-type tumor, lymph node metastasis was not observed. All of the 5-year survivors underwent curative resection and none of them had any positive surgical margin. Conclusion. Analysis of the clinicopathologic factors influencing the survival after surgical treatment showed that the macroscopic type, surgical curability, lymph node metastasis, tumor size, and cancer-free margin were the most predictive.     

Clinicopathologic features in patients with long-term survival following resection for intrahepatic cholangiocarcinoma

BACKGROUND/AIMS: As the overall prognosis for patients with intrahepatic cholangiocarcinoma is extremely poor, it is important to identify specific clinicopathologic features associated with long-term survival after hepatic resection for this tumor. METHODOLOGY: Of 54 patients who underwent hepatic resection for intrahepatic cholangiocarcinoma, 9 survived more than 5 years after surgery (survival group), while 28 patients died of recurrence within 3 years of surgery (early recurrence group). Clinicopathologic features were compared retrospectively between groups. RESULTS: Although clinical features in patients with long-term survival were similar to those in patients with early recurrence, lymphatic invasion, lymph node metastasis, intrahepatic metastasis and tumor involving the resection margin were more frequent in patients with early recurrence. CONCLUSIONS: Hepatic resection for intrahepatic cholangiocarcinoma without lymph node metastasis or intrahepatic metastasis offers hope for long-term survival.     

机器人与开腹手术治疗肝内胆管细胞癌患者近期疗效研究*

目的 比较机器人与传统开腹手术行肝叶切除术治疗肝内胆管细胞癌(ICC)患者的安全性和短期疗效。方法 2019年1月～2020年12月我院诊治的ICC患者27例,其中9例接受机器人手术,18例接受传统开腹肿瘤根治术,比较两组手术情况。结果 两组均完成肿瘤根治术;机器人组和开腹组患者手术时间【(198±32)分对(215±74)分】、术中出血量【200(100,250) ml对(275(200,300)ml】和术中输血次数(0次对2次)均无统计学差异(P>0.05);机器人组和开腹组患者肿瘤直径【4.0(2.5,5.5) cm 对6.3(3.9,6.5) cm】、R0切除率(100.0%对88.0%)和淋巴结转移率(44.4%对38.9%)比较,差异无统计学意义(P>0.05);机器人组术后卧床时间和住院日分别为2(1,2.5)d和7(4,8)d,显著短于开腹组【分别为3(1.8,3.5)d和11(8,12)d,P<0.05】,机器人组住院费用为11.3(9.1,13.5)万,与开腹组的10.1(8.8,11.5)万比,无统计学差异(P>0.05);两组术后并发症发生率为11.1%和27.8%,无统计学差异(P>0.05)。结论 开展机器人肿瘤根治术治疗ICC患者安全,术后恢复快。     

Surgery and chemotherapy for intrahepatic cholangiocarcinoma

Cholangiocarcinoma, arising from bile duct epithelium, is categorized into intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC), including hilarcholangiocarcinoma. Recently, there has been a worldwide increase in the incidence and mortality from ICC. Complete surgical resection is the only approach to cure the patients with ICC. However, locoregional extension of these tumors is usually advanced with intrahepatic and lymph-node metastases at the time of diagnosis. Resectability rates are quite low and variable (18%-70%). The five-year survival rate after surgical resection was reported to be 20%-40%. Median survival time after ICC resection was 12-37.4 mo. Only a small number of ICC cases, accompanied with ECC, gall bladder carcinoma, and ampullary carcinoma, have been reported in the studies of chemotherapy due to the rarity of the disease. However, in some reports, significant anti-cancer effects were achieved with a response rate of up to 40% and a median survival of one year. Although recurrence rate after hepatectomy is high for the patients with ICC, the residual liver and the lung are the main sites of recurrence after tentative curative surgical resection. Several patients in our study had a long-term survival with repeated surgery and chemotherapy. Repeated surgery, combined with new effective regimens of chemotherapy, could benefit the survival of ICC patients.     

Major hepatectomy for perihilar cholangiocarcinoma

Background/purpose

Hilar cholangiocarcinoma and intrahepatic cholangiocarcinoma involving the hepatic hilus are defined as “perihilar cholangiocarcinoma”. The principle of surgical treatment is hemi-hepatectomy or trisectionectomy of the liver, caudate lobectomy, and resection of the extrahepatic bile duct for complete resection of the tumor. The aim of this study was to review the outcomes of major hepatectomy for perihilar cholangiocarcinoma.

Methods

Using the Kaplan–Meier method and the Cox proportional hazards model, we analyzed the results in 125 patients with perihilar cholangiocarcinoma who had undergone major hepatectomy.

Results

Right hepatectomy, right trisectionectomy, left hepatectomy, and left trisectionectomy were performed in 66, 8, 49, and 2 patients, respectively. Curative resection was achieved in 79 patients (63.2%). Mortality and morbidity rates were 8.0 and 48.7%, respectively. The overall 1-, 3-, and 5-year survival rates of all patients were 73.2, 36.7, and 34.7%, respectively. The median survival was 26.8 months. Multivariate analysis showed that the independent prognostic factors for overall survival were gender, histopathological grading, curative resection, and American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) pT.

Conclusions

Major hepatectomy for perihilar cholangiocarcinoma was acceptable and showed satisfactory outcomes. For long-term survival in these patients, the surgeon should aim for complete resection of the tumor with negative margins.     

Liver transplantation for intrahepatic cholangiocarcinoma

The indication of liver transplantation for intrahepatic cholangiocarcinoma (ICC) is highly controversial. Initially, liver transplantation was embraced as a promising treatment for ICC, providing both a wider surgical margin and a potential cure for the underlying liver disease. However, the majority of transplant centers have abandoned liver transplantation for ICC due to poor long‐term survival and high recurrence rates. Interestingly, these decisions were based on studies with highly inconsistent outcomes due to a limited number of patients, various patient selection criteria, and the use of nonstandardized adjunctive therapy protocols. Indeed, recent studies have revealed that ICC patients with small solitary tumors have excellent long‐term survival after liver transplantation. Moreover, as seen in early‐stage hilar cholangiocarcinoma, neoadjuvant and adjuvant therapy hold promise for improved long‐term survival in patients with locally advanced ICC. As we work to expand treatment options for ICC, further evidence of success in this area is needed in order to justify the use of limited organ resources to treat ICC. Continued efforts to improve diagnosis of ICC, hone patient selection criteria, and implement standardized treatment protocols could provide certain patients with ICC access to potentially life‐saving liver transplantation.     

Surgical treatment for intrahepatic cholangiocarcinoma

Despite surgical treatment for intrahepatic cholangiocarcinoma (ICC) becoming more widely available, the prognosis after hepatic resection for ICC remains poor. Because ICC is relatively rare, the TNM staging system for ICC was finally established in the 2000s. Resection margin status and lymph node metastases are important prognostic factors after surgery for ICC; however, the true impact of wide resection margins or lymph node dissection on postoperative survival is unclear. Although adjuvant chemotherapy can improve the postoperative prognosis of patients with various types of cancer, no standard regimen has been developed for ICC. Over 50 % of patients suffer postoperative recurrence, even after curative resection, and no effective treatment for recurrent ICC has been established. Therefore, despite advances in imaging studies and hepatobiliary surgery, significant challenges remain in improving the prognosis of patients with ICC.